SMAD4 and neoplasm: An analysis of the presence of mutations of 105 genes in appendiceal cancers through the lens of the literature reviewed supports the view that in most of them, the inactivation of tumor suppressor genes, such as TP53 and SMAD4, is required in parallel with the reactivation of genes with oncogenic potentials, such as KRAS, GNAS, and BRAF, which support the main tumor processes, cell proliferation, angiogenesis, and evasion of apoptosis.